Effect of heat shock proteins on survival of isolated aortic cells from normal and atherosclerotic cynomolgus macaques.
Alterations in the level and distribution of arterial heat shock proteins (HSPs) have been demonstrated during atherogenesis. The significance of these changes within the developing and dying plaque, however, is not understood. To examine a potential protective effect of HSPs on arterial cells, enzymatically isolated cells from normal and diet-induced atherosclerotic aortas of cynomolgus macaques were stressed for 20 h with and without added 72/73 kDa heat shock proteins (HSP-72/73), over a range of temperatures and dosages. Cells were analyzed for changes in viability and lysosomal membrane integrity. The responses of cells from normal and diseased aortas for all test regimens were similar. Viability and lysosomal membrane integrity of untreated cells were correlated (r = 0.85), and both factors declined with increasing thermal stress (P less than 0.0005 and P less than 0.004, respectively). Exogenous HSP-72/73 increased cell viability after stress at a minimum concentration of 10 micrograms/ml (P less than 0.05) but was not concentration dependent. Response to different temperatures showed exogenous HSP-72/73 increased cell survival at all temperatures, with the greatest effect at 37 degrees C (P less than 0.01). In contrast, HSP-72/73 did not have an effect on lysosomal membrane integrity for the test period studied. The results demonstrate exogenous HSP-72/73 increases arterial cell survival, suggesting these proteins are associated with a protective mechanism in normal and diseased arteries.
Johnson
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AD
Department of Neurobiology and Anatomy, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.
Berberian
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PA
Bond
M G
MG
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006360:Heat-Shock Proteins / Q000494:pharmacology / Q000502:physiology*; D006358:Hot Temperature; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D008252:Macaca fascicularis; D008297:Male
D006360:Heat-Shock Proteins